Variants affected for cell surface differentiation antigens of lymphoid subpopulations, such as HLA-DR (Ia) and T cell antigens, will be isolated by immunoselection from cell lines of human B and T and other immunocompetent cells. Biochemical, immunologic and somatic cell genetic techniques will be used to analyze mechanisms of regulation of expression of these cell surface antigens. Analyses will include measurements of rates of synthesis and specific mRNA content, dominance-recessivity, cis- versus trans-active regulation and complementation analysis. Both loss variants and "up" variants will be isolated. Hybridomas producing monoclonal antibodies to cell surface antigens of immunocompetent cells will be produced. If appropriate variants are available, they will be used to screen hybridoma fluids for specific antibodies; if not, other strategies will be used for screening. Monoclonal antibodies produced will be used to select for further variants and as an aid in biochemical and immunologic characterization of the cell surface antigens and variant phenotypes.